Introduction to Neoplasia

Describe how neoplasms are named and classified

"-oma" tumor- usually benign "-carcinoma," "sarcoma" always malignant **"-OMAS" malignant by convention Lymphoma, mesothelioma, melanoma, seminoma

Describe the physical features of neoplastic cells

(benign neoplasms WELL differentiated, rarely graded) Malignant- graded: 1. Pleomorphism- variation in size or shape 2. Hyperchromatic staining- cells darker than normal, increased DNA 3. Nuclear/cytoplasmic ratio- more nucleus 4. Prominence of nuclei- gigantic prominent mitotic activity- high 5. disorganized growth- can't tell what it is

Tumors from Metaplastic Tissues: 3. Esophageal Cancer

-Chronic reflux of gastric acid into distal esophagus squamous epithelium --> gastric glandular epithelium Adenocarcinoma

Tumors from Metaplastic Tissues: 2. Cervical Cancer

-HPV columnar epithelium --infection-->squamous cell carcinoma

List the common names for benign and malignant tumors for the major types of tissue: MESENCHYMAL

-oma -sarcoma

Tumors from Metaplastic Tissues: 1. Lung Cancer

-smoking ciliated columnar epithelium to benign squamous epithelium -> progress to dysplasia (neoplastic change from now on) -> then carcinoma in situ -> then invasive squamous cell carcinoma

5. Explain why neoplasms often progressively become more aggressive 6. Explain why neoplastic cells usually displace normal cells

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Metastasis, desmoplasia

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Explain the meaning of GRADE with respect to differentiation and anaplasia versus STAGE with respect to extent of tumor

1. Grade- "how ugly it is" - Differentiation: degree to which neoplastic cells resemble normal cells -uglier it is and less like its tissue of origin, usually worse tumor behaves 2. Stage- extent of spread of a neoplasm

List the common names for benign and malignant tumors for the major types of tissue: HEMATOPOIETIC MALIG what three types?

1. Leukemias 2. Lymphomas 3. Multiple Myeloma

List the components of the neoplastic mass, i.e., the tumor cells versus the non-neoplastic support stroma [blood vessels, reactive fibroblasts]

1. Parenchymal component- mutated cell or cells which are undergoing unregulated proliferation 2. Stromal component- non-neoplastic cells which provide -vascular support and -framework of CT

Describe the growth characteristics of neoplastic cells: 1. benign 2. malignant

1. benign- grow slowly 2. malignant- grow more rapidly, -not shorter cell cycle, but more cells entering cell cycle, rate at which cellular replication exceeds cellular loss -shorter doubling time

Describe the mechanisms and pathways by which neoplasms may spread, including: 2. metastasis by lymphatics or blood vessels

1. direct seeding 2. spread through lymphatics or blood -invasion of vessels -embolization -growth in new location

Grades? Low, intermediate, high

1. low- WELL differentiated. look the same or nearly the same as tissue of origin 2. intermediate- some resemblance to tissue or origin 3. High- poorly differentiated or anaplastic- little or no similarity to original tissue anaplastic - The term anaplasia literally means "to form backward". It implies dedifferentiation, or loss of structural and functional differentiation of normal cells)

Accumulation of Mutations

1. neoplastic cells often have genetic instability --> additional mutations -> progress from dysplasia to invasive malignancy 2. chance of survival increases by large population of tumor cells...

Describe the mechanisms and pathways by which neoplasms may spread, including: 1. invasion- what does benign do? malignant?

Benign compresses Malignant- invades 1. decreased cell to cell adhesion - down regulate cadherin- fewer bridges -catenins- freeing of anchors of catenins into cytosol to drive cell division (dissociating cells causes cell proliferation) 2. malignant cells binding to ECM -ICAM, VCAM- aggressiveness -Integrins on cells bind to laminin and fibronectin of basement membrane -Integrin initiate penetration of bm by secretion of proteolytic enzymes: (1. --> serine proteinases, collagenases (metalloproteins) of type IV and I collagen (2. -->fibroblasts- DESMOPLASTIC REACTION - Type I collagenase - penetrate stroma -Migration through ECM and into metastasis 3. Migration -AMF causes Pseudopodia of cells rich in laminin and fibronectin receptors

Staging Low versus High?

Extent of spread: 1. Low- limited to site of origin, smaller the better prognosis 2. High- beyond organ of origin, larger the worse prognosis note: larger might have better therapies!

Cancer

General term for all malignant neoplasms

invasive carcinoma

Invasive through the basement membrane and/or metastases

List differences between Leukemia and Lymphomas

Leukemia- BLOOD AND BONE -myeloid or lymphoid hematopoietic stem cells -replace bone marrow -spill into peripheral blood - acute or chronic Lymphoma- IN SOLID TISSUE MASSES -malig of lymphocytes -do NOT spill into peripheral blood - Non and Hodgkin's

the main features of Multiple Myeloma, a plasmacytic neoplasm?

Malignant proliferation of Plasma Cells -remains in bone marrow - cause lesions in bone marrow - secrete MONOclonal IG's -pass into urine as BENCE-JONES protein (can cause renal failure)

Dysplasia

Neoplastic mutations which result abnormal features in some but not all original metaplastic cells so that there is a mixture of normal and abnormal cells

Carcinoma-in-situ

Neoplastic mutations which result in replacement of all normal epithelial cells by abnormal cells without invasion through the basement membrane

Define Neoplasm

New growth from uncontrolled or autonomous. uncontrolled proliferation as a result of GENETIC MUTATION. -called a neoplasm -can be benign or malignant

Metaplasia

Non-neoplastic change in type of tissue at a site of injury or irritation. (Not a neoplastic change, but a form of reaction to injury) -Associated with chronic irritation and explains cancers arising from cells not normally found in those sites

Three origins and two types of epithelial neoplasms?

Origin: ecto, meso, endodermal 1. cover surfaces- (benign) papilloma, (malig) carcinoma 2. glandular and ductal cells- (benign) adenoma/papilloma, (malig) adenocarcinoma

Tumor 1. benign 2. malignant

Swelling or mass from ANY cause (due to inflammation). Interchangeable term with neoplasm 1. Benign- (unchecked proliferations, abnormal maturation) -Do not invade surrounding tissues -Do not metastasize (travel to other organs) 2. Malignant-(unchecked proliferations, abnormal maturation) -Does invade surrounding tissue -Does metastasize

Staging system TMN cancer staging (not tested)

T size/extent of primary tumor N number and distribution of lymph node metastases M presence and extent of distant metastases

Explain why the Warbrug effect is useful for staging neoplasms

Tumor cells use a lot more glucose than normal cells: -Most tumor cells do not use mitochondria for glycolysis (normally make 20 ATP from 1 Glucose) -tumor skips mitochondria and make only 2 ATPS from 1 glucose (use more G than normal) -Radioactive labelled G taken up much more than surrounding normal tissues -Effect used for detecting tumors and their metastases

most famous pro-angiogenic factors?

VEGF bFGF

List the common names for benign and malignant tumors for the major types of tissue: MESENCHYMAL blood vessels?

benign- hemangioma, malig- angiosarcoma

List the common names for benign and malignant tumors for the major types of tissue: NERVOUS SYTEM nerve cells? melanocytes?

benign- neuroma/ganglioma, malignant- neuroblastoma/ medulloblastoma

List the common names for benign and malignant tumors for the major types of tissue: NERVOUS SYTEM melanocytes?

benign-nevus malignant- melanoma

List the common names for benign and malignant tumors for the major types of tissue: EPITHELIAL NEOPLASMS benign? malignant?

benign: papilloma malignant: carcinoma

Describe how metaplasia may cause a malignancy of a cell type arising at a site that does not usually have that cell type

ex: squamous epithelium replaces glandular epithelium = squamous epithelium -not neoplastic change but a form of reaction to an injury

List the common names for benign and malignant tumors for the major types of tissue: GERM CELLS germ cells? placenta? mixture?

germ cells benign-malignant sperm or ova malignant-seminoma, dysgerminoma placenta: benign-hyatidiform, malignant-choriocarcinoma Mixture of mature tissues: benign- mature teratoma malignant- immature teratoma (immature malignant embryonic tissue)

Describe the mechanisms and pathways by which neoplasms may spread, including: 3. role of angiogenesis

growth in new location requires angiogenesis Factors: 1. VEGF 2. bFGF Supress Anti-Angiogenic Factor 1. Thrombospondin-1

List the common names for benign and malignant tumors for the major types of tissue: NERVOUS SYSTEM-origin?

neuroectoderm

List differences between non-Hodgkins lymphoma vs Hodgkins lymphoma

non-Hodgkins lymphoma -do NOT have Reed-Sternberk (owl) cells -involve lymph nodes -cells show various stages of normal lymphocyte transformation -categorized as B or T cell vs Hodgkins lymphoma - REED-STERNBERG (owl) cells - giant multinucleated cells with large red nucleoli -involve lymph nodes -non-neoplastic host response -usually depress T cell function

Metastasis

separates from sites of tumor as a result of: -direct seeding of body cavities or surfaces -through lymphatic or blood

List the common names for benign and malignant tumors for the major types of tissue: MESENCHYMAL smooth muscle? skeletal?

sm- leiomyoma, -sarcoma skel-- rhabdomyoma, -sarcoma

Most famous anti-angiogenic factor which is frequently suppressed by tumor cells?

thrombospondin-1

Doubling Time

time required for tumor to double in size -higher grade, faster the growth, shorter doubling time

Why tumor cells generate angiotensis

to grow greater than 1mm? need blood supply